Antimicrobial Stewardship Practices in Outpatient Parenteral Antimicrobial Therapy Programs in the United States.

Background: Outpatient parenteral antimicrobial therapy (OPAT) regimens typically prioritize ease of antimicrobial administration, tolerability, safety, and accessibility over using the narrowest-spectrum antimicrobial. In light of this, OPAT providers often utilize different techniques to promote antimicrobial stewardship (AMS) in their OPAT programs. This study aims to characterize the AMS practices of OPAT programs across the United States that might meet The Joint Commission requirements for outpatient AMS metrics. Methods: This is a cross-sectional electronic survey of the Vizient AMS network. A total of 95 possible questions were designed to inquire about demographics, OPAT program structure, AMS initiatives, performance metrics, and resources. Results: Seventy-four survey responses were received, with 58 (78.4%) of the respondents indicating their institution offered OPAT services. Respondents reported having at least 1 AMS protocol and tracking at least 1 metric in 91% and 74% of OPAT programs, respectively. Only 40% of programs reported billing for OPAT-related services. Approximately 45% of respondents disagreed or strongly disagreed that their OPAT program had the resources needed to care for the population it serves. Respondents identified data analytics (69%), funding for expansion of services (67%), and pharmacists (62%) as resources of greatest need for their OPAT programs. Conclusions: This survey collectively describes the AMS practices currently employed by OPAT programs across the United States. The results provide specific examples of AMS initiatives, metrics, and resources that institutions may reference to advance the practices of their OPAT programs to meet The Joint Commission Outpatient Antimicrobial Stewardship standards.

Comparison of Sequential Dalbavancin With Standard-of-Care Treatment for Staphylococcus aureus Bloodstream Infections.

Background: Dalbavancin (DAL) is a long-acting lipoglycopeptide with activity against Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). This study investigates DAL as sequential therapy in S. aureus bloodstream infections (BSIs). Methods: We conducted a retrospective cohort study from 2014 to 2021 comparing sequential DAL with standard-of-care therapy (SoC) for S. aureus BSI. The primary outcome was 90-day clinical failure (90-day all-cause mortality or 90-day recurrence). Secondary outcomes were incidence of acute kidney injury, creatinine phosphokinase elevations, catheter-related thrombosis, and hospital-acquired infections. Analyses were adjusted using inverse probability of treatment weighting (IPTW). Results: Overall, 225 patients (45 DAL, 180 SoC) were included. DAL patients had a higher incidence of community-acquired infection and persons who use drugs; SoC patients had more comorbidities and a longer duration of bacteremia. MRSA incidence was similar between the DAL and SoC groups. The median length of stay was 16 days among DAL recipients compared with 24 days among SoC recipients. Central catheter placement was 17.8% compared with 57.2% in the SoC group. Ninety-day clinical failure occurred in 13.3% and 18.3% of participants in the DAL and SOC groups, respectively. In IPTW-adjusted analysis, sequential DAL was not associated with 90-day clinical failure (adjusted odds ratio, 0.94; 95% CI, 0.333-2.32). Conclusions: This study provides preliminary evidence that select patients with S. aureus BSI treated with sequential DAL have similar clinical failure rates, with significant reductions in catheter placement and hospital length of stay compared with SoC. Further prospective evaluation is needed.

Allowable room temperature excursions for refrigerated medications: A 20-year review.

PURPOSE: The aim of this review was to build upon previous literature describing the maximum duration for which refrigerated medications can tolerate room temperature excursions while maintaining stability and potency. METHODS: During a 12-month period ending in June 2021, the prescribing information and published monographs from multiple pharmacy compendia were reviewed for all medications and biologic products approved by the US Food and Drug Administration (FDA) for human use since January 2000. Products that were subsequently withdrawn from the US market were excluded. When temperature excursion data was unavailable in published form, product manufacturers were surveyed via telephone and/or email. Acceptable storage information for all products for which storage is recommended at temperatures below room temperature (20-25 °C [68-77 °F]) was compiled and arranged in tabular format. RESULTS: Of the 705 products or formulations approved by FDA during the predefined time period, 246 were identified as requiring storage at temperatures below room temperature. After review of available prescribing information and manufacturer communications, if applicable, acceptable periods of excursion to temperatures at room temperature or higher were identified for 214 products (87%). CONCLUSION: Information related to acceptable periods of room temperature excursion was compiled for a total of 214 products approved for US distribution since 2000. The included tables may increase patient safety and decrease medication loss or related expenditures.

Immediate Hypersensitivity to Fluoroquinolones: A Cohort Assessing Cross-Reactivity.

Background: Fluoroquinolones are the second-most prescribed antimicrobial and are frequently associated with causing hypersensitivity reactions. Existing evidence regarding cross-reactivity of fluoroquinolones is limited, offering clinicians little guidance in understanding the implications of selecting an in-class alternative among patients with histories of allergic reactions to fluoroquinolones. The aim of this study was to compare the frequency of immediate hypersensitivity reactions to ciprofloxacin, levofloxacin, and/or moxifloxacin among patients with a history of immediate hypersensitivity to a different fluoroquinolone. Methods: This retrospective chart review included adult patients with a history of an immediate hypersensitivity reaction to ciprofloxacin, levofloxacin, and/or moxifloxacin and a documented prescription for a different fluoroquinolone. The primary outcome was documentation of a hypersensitivity reaction upon second fluoroquinolone exposure. Results: A total of 321 cases met inclusion criteria. Of these cases, 2.5% experienced an immediate hypersensitivity reaction after second fluoroquinolone exposure to ciprofloxacin, levofloxacin, and/or moxifloxacin. Within the ciprofloxacin, levofloxacin, and moxifloxacin index allergy cohorts, the frequency of cross-reactivity was 2.5%, 2.0%, and 5.3%, respectively. Conclusions: Our data suggest that patients with a history of immediate hypersensitivity reaction to ciprofloxacin, levofloxacin, and/or moxifloxacin are at low risk of experiencing a cross-reaction when exposed to a different fluoroquinolone. Avoidance of all fluoroquinolones in this patient population may not be warranted.

A comprehensive simulation-based assessment of office building performance adaptability to teleworking scenarios in different Canadian climate zones.

Recent studies have shown that office building systems do not adapt well to partial occupancy (e.g., from teleworking) and thus perform suboptimally. As a result, this study aims to assess office building performance adaptability by investigating the impact of four different technologies, including occupancy-based lighting, smart plugs (occupancy-based plug load), demand-controlled ventilation (DCV), occupancy-based thermostat, and their cumulative effect in office buildings in six different Canadian climates. A three-story office building is simulated in EnergyPlus version 9.3.0 under five occupancy scenarios, including 0% occupancy, 100% occupancy, 50% uniformly distributed occupancy across the floor, 50% consolidated occupancy scenario where occupants work in core zones, and 50% consolidated occupancy scenario where occupants work in perimeter zones. The results are compared using energy use intensity (EUI), energy use intensity per occupant (EUP), and the corresponding greenhouse gas (GHG) emissions. A total of 180 simulations demonstrate the occupancy-adaptive technologies are generally most beneficial for low occupancy scenarios and milder climates. The results also show the cumulative impact of all these technologies on the potential energy savings is significant in the climates under consideration. Overall, the results show office buildings can improve their performance adaptability during partial occupancy by implementing the studied technologies. Aside from filling in the current knowledge gap in the literature on partial occupancy, the for the first time results of this study systemically demonstrate how each technology performs under different partial occupancy scenarios and how they perform together at each climate.

Discovery of imidazopyridines containing isoindoline-1,3-dione framework as a new class of BACE1 inhibitors: Design, synthesis and SAR analysis.

Alzheimer's disease is characterized by chronic neurodegeneration leading to dementia. The main cause of neurodegeneration is considered to be the accumulation of amyloid-ß. Inhibiting BACE1 is a well-studied approach to lower the burden of amyloid-ß aggregates. We designed a series of imidazopyridines-based compounds bearing phthalimide moieties as inhibitors of BACE1. The compounds 8a-o were synthesized by the Groebke-Blackburn-Bienaymé three-component reaction of heteroaromatic amidines, aldehydes and isocyanides. Evaluating the BACE1 inhibitory effects of the synthesized compounds revealed that introducing an aminocyclohexyl moiety in the imidazopyridine core resulted in a significant improvement in its BACE1 inhibitory potential. In this regard, compound 8e was the most potent against BACE1 with an IC50 value of 2.84 (±0.95) µM. Molecular docking revealed that the nitrogen atom of imidazopyridines and the oxygen atom of the phenoxypropyl linker were involved in hydrogen bound interactions with Asp228 and Asp32 of BACE1 active site, respectively. The phthalimide moiety oriented toward the flap pocket and interacted with phe108, lle110, Trp115, Ile118 through van der Waal's and hydrophobic interactions. These findings demonstrate that imidazopyridines-based compounds bearing phthalimide moiety have the potential to decrease amyloid-ß levels and ameliorate the symptoms of Alzheimer's disease.

Prophylactic efficacy of primaquine for preventing Plasmodium falciparum and Plasmodium vivax parasitaemia in travelers: A meta-analysis and systematic review.

BACKGROUND: With increased international travel over the world the need for safe and effective chemoprophylaxis for malaria is as great as ever. The choice of regimen is difficult, as effectiveness should be weighted against potential adverse effects. Although, some studies have reported high prophylactic efficacy of primaquine, there is no comprehensive evidence comparing its prophylactic effectiveness as well as toxicity. To fill the gap, this systematic review and meta-analysis study was carried out. METHODS: Using MeSH terms, 756 records were detected through searching "Pubmed", "Embase","Web of Science"and "Cochrane" databases. From these,7 relevant full-text articles with 14 comparisons for final quantitative meta-analysis were included in our review. In order to make a comparison between the studies, Risk Ratios(RRs) and their 95% confidence intervals(CIs) were estimated. RESULTS: Overall,74% reduction in the incidence of parasitaemia by primaquine versus other prophylactic regimens was estimated(RRoverall = 0.26, CI 95%:0.16-0.41--RRvivax = 0.16, CI 95%:0.07-0.36--RRfalciparum = 0.31, CI 95%:0.18-0.55). The incidence rate ratios for adverse effects showed no statistically significant difference between primaquine and control groups (p > 0.05). CONCLUSIONS: For persons without G6PD deficiency, who are not pregnant, primaquine is the most effective presently available prophylactic for P. vivax malaria and comparable to such regimens as doxycycline, mefloquine and atovaquone-proguanil for the prevention of P. falciparum malaria.

Disturbance-free rapid solution exchange for magnetic tweezers single-molecule studies.

Single-molecule manipulation technologies have been extensively applied to studies of the structures and interactions of DNA and proteins. An important aspect of such studies is to obtain the dynamics of interactions; however the initial binding is often difficult to obtain due to large mechanical perturbation during solution introduction. Here, we report a simple disturbance-free rapid solution exchange method for magnetic tweezers single-molecule manipulation experiments, which is achieved by tethering the molecules inside microwells (typical dimensions-diameter (D): 40-50 µm, height (H): 100 µm; H:D∼2:1). Our simulations and experiments show that the flow speed can be reduced by several orders of magnitude near the bottom of the microwells from that in the flow chamber, effectively eliminating the flow disturbance to molecules tethered in the microwells. We demonstrate a wide scope of applications of this method by measuring the force dependent DNA structural transitions in response to solution condition change, and polymerization dynamics of RecA on ssDNA/SSB-coated ssDNA/dsDNA of various tether lengths under constant forces, as well as the dynamics of vinculin binding to α-catenin at a constant force (< 5 pN) applied to the α-catenin protein.

Buried centimeter-long micro- and nanochannel arrays in porous silicon and glass.

We developed a simple process to fabricate deeply buried micro- and nanoscale channels in glass and porous silicon from bulk silicon using a combination of ion beam irradiation, electrochemical anodization and high temperature oxidation. The depth, width and length of these structures can be controllably varied and we successfully fabricated an array of centimeter-long buried micro- and nanochannels. This process allows densely packed, arbitrary-shaped channel geometries with micro- to nanoscale dimensions to be produced in a three-dimensional multilevel architecture, providing a route to fabricate complex devices for use in nanofluidics and lab-on-a-chip systems. We demonstrate the integration of these channels with large reservoirs for DNA linearization in high aspect ratio nanochannels.

Tuning the interface conductivity of LaAlO3/SrTiO3 using ion beams: implications for patterning.

Patterning of the two-dimensional electron gas formed at the interface of two band insulators such as LaAlO3/SrTiO3 is one of the key challenges in oxide electronics. The use of energetic ion beam exposure for engineering the interface conductivity has been investigated. We found that this method can be utilized to manipulate the conductivity at the LaAlO3/SrTiO3 interface by carrier localization, arising from the defects created by the ion beam exposure, eventually producing an insulating ground state. This process of ion-beam-induced defect creation results in structural changes in SrTiO3 as revealed by the appearance of first-order polar TO2 and TO4 vibrational modes which are associated with Ti-O bonds in the Raman spectra of the irradiated samples. Furthermore, significant observation drawn from the magnetotransport measurements is that the irradiated (unirradiated) samples showed a negative (positive) magnetoresistance along with simultaneous emergence of first-order (only second order) Raman modes. In spectroscopic ellipsometry measurements, the optical conductivity features of the irradiated interface are broadened because of the localization effects, along with a decrease of spectral weight from 4.2 to 5.4 eV. These experiments allow us to conclude that the interface ground state (metallic/insulating) at the LaAlO3/SrTiO3 can be controlled by tailoring the defect structure of the SrTiO3 with ion beam exposure. A resist-free, single-step direct patterning of a conducting LaAlO3/SrTiO3 interface has been demonstrated. Patterns with a spatial resolution of 5 µm have been fabricated using a stencil mask, while nanometer scale patterns may be possible with direct focused ion beam writing.

Silicon-based photonic crystals fabricated using proton beam writing combined with electrochemical etching method.

A method for fabrication of three-dimensional (3D) silicon nanostructures based on selective formation of porous silicon using ion beam irradiation of bulk p-type silicon followed by electrochemical etching is shown. It opens a route towards the fabrication of two-dimensional (2D) and 3D silicon-based photonic crystals with high flexibility and industrial compatibility. In this work, we present the fabrication of 2D photonic lattice and photonic slab structures and propose a process for the fabrication of 3D woodpile photonic crystals based on this approach. Simulated results of photonic band structures for the fabricated 2D photonic crystals show the presence of TE or TM gap in mid-infrared range.

Fabrication of concave silicon micro-mirrors.

We have fabricated spherical and cylindrical concave micro-mirrors in silicon with dimensions from 20 microm to 100 microm. The fabrication process involves standard photolithography followed by large area ion beam irradiation and electrochemical anodisation in a HF electrolyte. After thermal oxidation the silicon surface roughness is less than 2 nm. We also present a multilayer porous silicon distributed Bragg reflector fabricated on concave silicon surfaces which selectively reflect and focus a band of wavelengths from a parallel beam of incident white light. Development of such low roughness concave microstructures opens up new applications in areas such as silicon photonics and quantum information science.